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Editorial illustration for the Prognyx briefing on loncastuximab tesirine (ZYNLONTA) plus glofitamab, CD19 antibody-drug conjugate + CD20 x CD3 bispecific antibody

Briefing · From the Watchtower

ZYNLONTA plus glofitamab posts 88.7% response rate in relapsed DLBCL before ASH

By · Founder, Prognyx ● Sourced to primary records Oncology
In brief: ADC Therapeutics will present Phase 1b LOTIS-7 data at the 68th ASH Annual Meeting showing ZYNLONTA (loncastuximab tesirine) plus glofitamab produced an 88.7% overall response rate and a 75.3% complete response rate across 97 efficacy-evaluable relapsed or refractory DLBCL patients. The company calls it its most compelling combination data to date in second-line-plus DLBCL and is assessing a Phase 3 trial and a Breakthrough Therapy request, even as its separate ZYNLONTA-plus-rituximab combination (LOTIS-5) drew FDA benefit-risk concerns over an imbalance in Grade 5 events.

ADC Therapeutics will bring Phase 1b LOTIS-7 data to the 68th American Society of Hematology Annual Meeting in December 2026 showing that ZYNLONTA (loncastuximab tesirine) combined with glofitamab produced an 88.7% overall response rate and a 75.3% complete response rate across 97 efficacy-evaluable relapsed or refractory DLBCL patients [1]. The company disclosed the top-line figures in a 4 November 2026 abstract announcement, part of five oral presentations and several posters covering the ZYNLONTA program [1].

The numbers matter because of where ZYNLONTA sits today. A 75.3% complete response rate in combination, if it survives full data, is the kind of result that pushes an asset toward earlier lines rather than keeping it a late-line single agent.

Management is leaning into that read. Its 13 August 2026 8-K reported LOTIS-7 enrollment complete at 100 patients on the selected 150 µg/kg ZYNLONTA starting dose, called the combination "the most compelling combination data generated to date in 2L+ DLBCL," and said it is assessing a Phase 3 trial and plans to seek Breakthrough Therapy designation [3].

The other combination is the reason to read this carefully

ADC ran two combination bets in parallel, and they are diverging. LOTIS-5 pairs ZYNLONTA with rituximab. After the pre-sBLA FDA meeting, the agency "noted substantial concerns regarding the benefit-risk or verification of clinical benefit observed in this trial based on the imbalance in Grade 5 events, when assessed in the context of a marginal treatment benefit," and the company is now assessing the best regulatory path for that trial [3]. Grade 5 events are fatal ones. So the glofitamab combination now carries the company's combination thesis, and the ASH data is the proof point that has to land.

Who is exposed

Second-line-plus DLBCL is crowded. MONJUVI (tafasitamab-cxix) with lenalidomide competes directly in the same relapsed or refractory DLBCL setting for patients ineligible for autologous stem cell transplant [9]. CD19 CAR-T cells YESCARTA (axicabtagene ciloleucel) [7] and BREYANZI (lisocabtagene maraleucel) [8] occupy the aggressive relapsed setting. On the pipeline side sit CD20 bispecifics and cell therapies: Genmab's epcoritamab in a Phase 3 trial that is active but no longer recruiting (NCT04628494) [10], Regeneron's odronextamab in a Phase 3 trial in previously untreated DLBCL now recruiting toward 904 patients (NCT06091865) [11], and Lyell Immunopharma's dual CD19/CD20 CAR-T rondecabtagene autoleucel in a Phase 3 trial against investigator's choice CD19 CAR-T, recruiting toward 400 patients (NCT07188558) [12]. No public head-to-head pits any of these against the 88.7% LOTIS-7 figure; cross-trial comparison in different populations is not an efficacy ranking.

What to watch next

It should carry what an abstract headline cannot: durability, progression-free survival, and the safety profile of a CD19 ADC stacked on a CD20 bispecific, the exact axis on which LOTIS-5 ran into trouble. The Phase 3 design, its trial identifier, and any Breakthrough Therapy filing are not yet public.

The now-what

For a competing DLBCL or BD operator, three moves are on the table. Treat the December readout as a diligence gate, not a done deal, and withhold any repositioning until the safety and PFS tables are in hand. If you run a CD20 bispecific or a cell therapy in second line, model a combination ADC entrant one dose-finding cycle behind and pressure-test your own program's complete response bar against 75.3%. And read LOTIS-5 as the live risk on the whole class: the FDA concern was fatal-event imbalance against marginal benefit, which is a combination-safety question that will follow any ZYNLONTA pairing into the clinic.

What Prognyx could not verify

The Phase 3 glofitamab trial has no public identifier or start date in the record, and the Breakthrough Therapy request is stated intent rather than a confirmed filing [3]. Full safety, durability, and progression-free survival for LOTIS-7 are not in the abstract disclosure and await the December presentation.

Threat level: moderate and rising for second-line DLBCL programs. Window to act: before the full ASH readout in December 2026.

Questions this briefing answers

What did ADC Therapeutics report for ZYNLONTA plus glofitamab?

In Phase 1b LOTIS-7, the combination produced an 88.7% overall response rate and a 75.3% complete response rate across 97 efficacy-evaluable relapsed or refractory DLBCL patients, disclosed in the 4 November 2026 ASH abstract announcement [1]. Full data are scheduled for the 68th ASH Annual Meeting in December 2026 [4].

How does this differ from ADC Therapeutics' LOTIS-5 program?

LOTIS-5 pairs ZYNLONTA with rituximab and is distinct from the glofitamab combination. After the pre-sBLA FDA meeting, the agency raised benefit-risk concerns over an imbalance in Grade 5 (fatal) events against a marginal treatment benefit, and ADC Therapeutics is reassessing that trial's regulatory path [3].

Sources: every claim traces to the primary record

  1. PR Newswire: ADC Therapeutics ASH 2026 abstracts release
  2. ClinicalTrials.gov NCT04970901 (LOTIS-7)
  3. SEC 8-K (Exhibit 99.1), 13 August 2026
  4. SEC 8-K (Exhibit 99.1), restructuring release
  5. FDA label (DailyMed): ZYNLONTA
  6. Drugs@FDA: BLA 761196 (ADC Therapeutics SA)
  7. FDA label (DailyMed): YESCARTA
  8. FDA label (DailyMed): BREYANZI
  9. FDA label (DailyMed): MONJUVI
  10. ClinicalTrials.gov NCT04628494 (epcoritamab Phase 3)
  11. ClinicalTrials.gov NCT06091865 (odronextamab Phase 3)
  12. ClinicalTrials.gov NCT07188558 (rondecabtagene autoleucel Phase 3)

How this briefing was produced: Drafted and audited by the Prognyx engine against the primary sources cited above, then published automatically for clearing the audit threshold set by Rali Filali. Below that threshold, a briefing is not published. The full method.

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Prognyx briefings are built from public information and reflect Prognyx's analysis. They are not investment advice and do not promote any product or off-label use.